The purpose of this Notice is to clarify that the scope of the funding opportunity announcement (FOA) PA-13-161, as described in the announcements, remains unchanged, but the section on “Medications Development for the Treatment of Alcohol Use disorders and Alcohol-Induced Tissue Damage” is replaced as follows:

Part 2. Section I. Funding Opportunity Description

1. Medications Development for the Treatment of Alcohol Use Disorders and Alcohol-Induced Tissue Damage
Efforts to develop medications for alcohol use disorders have expanded rapidly in recent years. Three agents—disulfiram, naltrexone, and acamprosate—are now approved for use in the United States and many other countries. However, because of the heterogeneous nature of alcohol use disorders, many patients have limited or no response to these medications. Therefore, developing new medications and evaluating their use in combination with other medications and with behavioral therapies are important steps toward improving treatment outcomes for all individuals with alcohol use disorders. Applications that propose standard efficacy trials of widely-studied and well-characterized medications such as naltrexone, topiramate, acamprosate, varenicline, ondansetron, gabapentin, baclofen, and disufiram in alcohol dependent subjects will not be considered. The collection of genetic samples and the use of biomarkers, particularly the ethanol metabolites ethyl glucuronide and phosphatidylethanol to verify drinking, are encouraged.

Advances also have been made in understanding the mechanisms of alcohol-induced tissue damage. Oxidative stress and inflammation play a major role in the pathogenesis of alcohol-associated injuries of various organs, including the liver, pancreas, heart, lungs, brain, and peripheral nervous system. Potential therapeutic agents include those that attenuate the actions of pro-inflammatory cytokines (e.g., the tumor necrosis factor (TNF)-a), and antioxidants (e.g., S-adenosyl-L-methionine (SAMe), glutathione, and vitamins A and E). Other potential new treatments of alcoholic liver disease include cannabinoid CB1 antagonists and CB2 agonists, metformin (an insulin-sensitizing agent), antifibrotic agents, prebiotics, probiotics, and zinc.

Finally, to improve safety, efficacy, and efficiency of medications, it is important to identify and characterize patients who respond positively to the medications and those who experience adverse events.

Specific areas of research include, but are not limited to, the following examples:

Discover, develop, and test new, more effective agents to prevent or reduce drinking.

Discover and develop medications to reduce smoking in alcohol-abusing individuals.

Discover and develop novel medications to treat alcohol-induced organ damage by attenuating or reversing the tissue damage. Identifying new targets for drug development based on mechanisms underlying the alcohol-induced damage is encouraged.